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| 題名: | Sumoylation of p45/NF-E2: Nuclear positioning and transcriptional activation of the mammalian beta-like globin gene locus |
| 作者: | Shyu, YC;Lee, TL;Ting, CY;Wen, SC;Hsieh, LJ;Li, YC;Hwang, JI;Lin, CC;Shen, CKJ |
| 貢獻者: | 附設醫院醫研部;Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan;Natl Yang Ming Univ, Inst Genet, Taipei 112, Taiwan;Natl Def Univ, Inst Life Sci, Taipei, Taiwan;NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA;China Med Univ Hosp, Dept Med Res, Taichung, Taiwan;Chung Shan Med & Dent Coll, Dept Biomed Sci, Taichung, Taiwan |
| 日期: | 2005 |
| 上傳時間: | 2010-09-24 15:00:32 (UTC+8) |
| 出版者: | AMER SOC MICROBIOLOGY |
| 摘要: | 1-(3.4-Diniethoxyphenyl)-3,5-dodecenedione (16), a gingerdione derivative, was synthesized in our laboratory, has been demonstrated to be an effective anti-tumor agent in human leukemia cells. Gingerdione is one of the components from ginger. In the present study, we found that 16 could inhibit cell proliferation in the time- and dose-dependent manner in human promyelocytic leukemia HL-60 cells. To investigate the anti-proliferation mechanism of 16, cell cycle analysis was performed. Results showed that 16 induced significant G I arrest and apoptosis in HL-60 cells. It was proved by the reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of regulatory on G I arrest that the levels of p 15 and p27 increased after treatment and mRNA levels of cyclin D2, cyclin E, and cdc25A were decreased. The 16-induced apoptosis was further confirmed by DNA fragmentation assay. The DNA gel electrophoresis showed that 16 induced DNA fragmentation, a biochemical hallmark of apoptosis, in HL-60 cells. 16-induced apoptosis was accompanied by an apparent up-regulation of caspase-3. and down-regulation of Bcl-2. Taken together, these results suggest that markedly down-regulation of G I associated cyclin D2, cyclin E and cdc25A and up-regulation of CDKI, p15 and p27, and may contribute to 16-mediated cell cycle arrest. Furthermore, the Bcl-2 expression decrease and caspase-3 activation may be the plausible mechanism by which 16 induced apoptosis. These results suggest that 16 is a potent anti-HL-60 drug and possess a significant action on cell cycle before commitment for apoptosis occurrence. (C) 2005 Elsevier Ltd. All rights reserved. |
| 關聯: | MOLECULAR AND CELLULAR BIOLOGY 25(23):10365-10378 |
| 顯示於類別: | [台中附設醫院] 期刊論文
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